tbuckley/cabot-search huggingface dataset:
Control of immediate early gene expression by CPEB4-repressor complex-mediated mRNA degradation
Authors: Fabian Poetz, Svetlana Lebedeva, Johanna Schott, Doris Lindner, Uwe Ohler, Georg Stoecklin
Journal: Genome biology (2022)

Abstract Background Cytoplasmic polyadenylation element-binding protein 4 (CPEB4) is known to associate with cytoplasmic polyadenylation elements (CPEs) located in the 3′ untranslated region (UTR) of specific mRNAs and assemble an activator complex promoting the translation of target mRNAs through cytoplasmic polyadenylation. Results Here, we find that CPEB4 is part of an alternative repressor complex that mediates mRNA degradation by associating with the evolutionarily conserved CCR4-NOT deadenylase complex. We identify human CPEB4 as an RNA-binding protein (RBP) with enhanced association to poly(A) RNA upon inhibition of class I histone deacetylases (HDACs), a condition known to cause widespread degradation of poly(A)-containing mRNA. Photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) analysis using endogenously tagged CPEB4 in HeLa cells reveals that CPEB4 preferentially binds to the 3′UTR of immediate early gene mRNAs, at G-containing variants of the canonical U- and A-rich CPE located in close proximity to poly(A) sites. By transcriptome-wide mRNA decay measurements, we find that the strength of CPEB4 binding correlates with short mRNA half-lives and that loss of CPEB4 expression leads to the stabilization of immediate early gene mRNAs. Akin to CPEB4, we demonstrate that CPEB1 and CPEB2 also confer mRNA instability by recruitment of the CCR4-NOT complex. Conclusions While CPEB4 was previously known for its ability to stimulate cytoplasmic polyadenylation, our findings establish an additional function for CPEB4 as the RNA adaptor of a repressor complex that enhances the degradation of short-lived immediate early gene mRNAs.
34785 Epidermal reconstruction during ex vivo confocal microscopy for detection of superficial basal cell carcinoma with 3D-mosaicking and intensity projection
Authors: Karon Millar, Ucalene Harris, Alex Bang, Matthew Moronta, Mercedes Martín Sendín, Anthony Rossi, Erica Lee, Kishwer Nehal, Milind Rajadhyaksha, Kivanc Kose, Manu Jain
Journal: Journal of the American Academy of Dermatology (2022)
33226 Analysis of histologic and molecular improvement in moderate-to-severe psoriasis: Results from a phase 1b trial of the novel allosteric Tyk2 inhibitor NTX-973
Authors: Joshua J. McElwee, Sandra Garcet, Xuan Li, Inna Cueto, Norma Kunjravia, Darshna Rambhia, Bhaskar Srivastava, James G. Krueger
Journal: Journal of the American Academy of Dermatology (2022)
34115 Real-life efficacy and safety of biologic treatment in patients with moderate to severe psoriasis and previous diagnosis of a malignant tumor: Single-center descriptive study
Authors: Antonio José Durán Romero, Lourdes Rodríguez Fernández Freire, Mercedes Sendín Martín, Juan Ortiz Álvarez, Juan Carlos Hernández Rodríguez, Julián Conejo-Mir Sánchez
Journal: Journal of the American Academy of Dermatology (2022)
32824 Factors associated with treatment satisfaction in atopic dermatitis: A cross-sectional, population-based study examining patient and physician perspectives
Authors: Zelma C. Chiesa Fuxench, Eva Nee, Eric Simpson, Wendy Smith Begolka, Mark Boguniewicz, Luz Fonacier, Joel M. Gelfand, Mitchel Grayson, David J. Margolis, Jonathan Silverberg, Peck Ong
Journal: Journal of the American Academy of Dermatology (2022)
33991 Predictors of response to secukinumab in patients with moderate to severe plaque psoriasis with special area involvement in real-world clinical setting: A pooled analysis of prospective observational studies PROSPECT, SERENA, and REALIA
Authors: Diamant Thaci, Peter Foley, Craig Richardson, Yulin Shi, Juanzhi Fang, Matthias Augustin
Journal: Journal of the American Academy of Dermatology (2022)
33563 Change in Cutibacterium acnes phylotype diversity and improvement of clinical parameters using a new dermocosmetic product containing Myrtus communis and Celastrol-enriched plant cell culture extracts in patients with acne vulgaris
Authors: Valerie Mengeaud, Celine Mias, Marie-Dominique Thouvenin
Journal: Journal of the American Academy of Dermatology (2022)
Comparative analyses of vertebrate CPEB proteins define two subfamilies with coordinated yet distinct functions in post-transcriptional gene regulation
Authors: Berta Duran-Arqué, Manuel Cañete, Chiara Lara Castellazzi, Anna Bartomeu, Anna Ferrer-Caelles, Oscar Reina, Adrià Caballé, Marina Gay, Gianluca Arauz-Garofalo, Eulalia Belloc, Raúl Mendez
Journal: Genome biology (2022)

Vertebrate CPEB proteins bind mRNAs at cytoplasmic polyadenylation elements (CPEs) in their 3' UTRs, leading to cytoplasmic changes in their poly(A) tail lengths; this can promote translational repression or activation of the mRNA. However, neither the regulation nor the mechanisms of action of the CPEB family per se have been systematically addressed to date.
34751 Association between rosacea and eye diseases in patients with diabetes: A nationwide cohort study
Authors: Fang-Ying Wang, Eugene Yu-Chuan Kang, Chun-Hao Liu, Chau Yee Ng, Shih-Chieh Shao, Edward Chia-Cheng Lai, Wei-Chi Wu, Yi-You Huang, Kuan-Jen Chen, Chi-Chun Lai, Yih-Shiou Hwang
Journal: Journal of the American Academy of Dermatology (2022)
35163 Ruxolitinib cream provided progressive improvement in patients with atopic dermatitis who did not achieve Investigator’s Global Assessment treatment success at week 8: Pooled results from 2 phase 3 studies
Authors: Lawrence F. Eichenfield, Andrew Blauvelt, Leon Kircik, May E. Venturanza, Haobo Ren, Eric L. Simpson
Journal: Journal of the American Academy of Dermatology (2022)
34675 Antinuclear antibodies detection in rosacea phenotypes
Authors: David A. Castillo Molina, Jorge Andres Rios-Duarte, Jesus Daniel Fierro-Lozada, Maria J. Sanchez-Zapata, Sara Muñoz-Ordoñez, Criss Madeley Millan-Puerto, Ana Maria Garcia-Concha, Claudia Vanesa Cera-Coll
Journal: Journal of the American Academy of Dermatology (2022)
33542 Stability of response prior to baricitinib downtitration or treatment withdrawal: Outcome from a substudy of BREEZE AD3
Authors: Jonathan Silverberg, Robert Bissonnette, Kenji Kabashima, Nosbaum Audrey, Susan Ball, Tracy Cardillo, Luna Sun, Yun-Fei Chen, Thomas Bieber
Journal: Journal of the American Academy of Dermatology (2022)
33130 Effect of tildrakizumab on work/study-related productivity: Pooled analysis from reSURFACE 1 and reSURFACE 2 phase 3 trials
Authors: Matthias Augustin, Ulrich Mrowietz, Kristian Gaarn Du Jardin, Ismail Kasujee, Esteban Daudén
Journal: Journal of the American Academy of Dermatology (2022)
32236 Safety of ixekizumab in adult patients with moderate-to-severe psoriasis: Data from 15 clinical trials with over 18,000 patient-years of exposure
Authors: Christopher E.M. Griffiths, Melinda Gooderham, Jean-Frederic Colombel, Tadashi Terui, Ana P. Accioly, Gaia Gallo, Danting Zhu, Andrew Blauvelt
Journal: Journal of the American Academy of Dermatology (2022)
32378 Comorbidities, demographic and clinical features of patients with alopecia areata in a dermatologic center in Bogota, Colombia
Authors: David A. Castillo Molina, Jesus Daniel Fierro-Lozada, Maria J. Sánchez-Zapata, Winnie Joanne Celorio-Murillo, Ana María García-Concha, Natalia Muñoz-Angulo, Paula Andrea Chacón-Jaramillo, David Ernesto Castillo Saavedra
Journal: Journal of the American Academy of Dermatology (2022)
33537 Inhibitory effects of ME3183, a novel phosphodiesterase-4 inhibitor, on stimulants-induced production of proinflammatory cytokines and chemokines in whole blood cell cultures of patients with plaque psoriasis
Authors: Chizuko Kaji, Kenji Suzuki, Akiko Kano
Journal: Journal of the American Academy of Dermatology (2022)

Inhibition of phosphodiesterase-4 (PDE4) has been reported as a therapeutic target for inflammatory diseases. ME3183 is an orally available and selective inhibitor of PDE4, which showed various anti-inflammatory effects in nonclinical studies. We examined the inhibitory effects of ME3183 on stimulants-induced production of proinflammatory cytokines and chemokines in whole blood cell cultures of healthy volunteers and patients with plaque psoriasis (Ps). Tumor necrosis factor alpha (TNF-α), interleukin 17A, interferon-γ, monocyte chemotactic protein-1 and interferon gamma-induced protein-10 were measured in each subject's whole blood cell cultures stimulated with lipopolysaccharide (LPS) or phytohemagglutinin (PHA) in the presence of ME3183 or apremilast. Correlation between the inhibition of TNF-α production and each clinical parameter of patients were statistically analyzed. ME3183 showed approximately 5- to 40-folds more potent inhibitory activities against production of cytokines than apremilast both in the whole blood cell cultures of Ps patients and healthy subjects. Interestingly, our correlation analysis suggested that high body surface area (%) and long-duration of psoriasis may be associated with the potency (IC50) of ME3183 against TNF-α production. ME3183 showed higher potency than apremilast in the inhibition of proinflammatory cytokines and chemokines production. ME3183 can be a new generation of PDE4 inhibitor with improved therapeutic effect, and the efficacy of ME3183 will be investigated in patients with Ps in the P2a study.
35101 Combination treatment of transdermal micro-jet using Er:YAG laser and ablative fractional 10,600-nm carbon dioxide laser for acne scar
Authors: Dong Hye Suh, Hyung Seob Kim, Hyun-Joo Kim, Dermatology, Sang Jun Lee, Kye-Yong Song, Min Kyung Shin
Journal: Journal of the American Academy of Dermatology (2022)
32496 Efficacy and safety of abrocitinib according to geographies
Authors: Andrew F. Alexis, Zakiya P. Rice, Kenji Kabashima, Paula C. Luna, Jacob P. Thyssen, Magdalena Trzeciak, Pinaki Biswas, Gary L. Chan, Erman Güler, Mark Levenberg
Journal: Journal of the American Academy of Dermatology (2022)
33006 Long-term improvement of patient-reported outcomes in adult patients with atopic dermatitis treated with baricitinib in the US and Canada
Authors: Zelma C. Chiesa Fuxench, April W. Armstrong, Joseph F. Merola, Rocco T. Serrao, Robinette Angle, Evangeline J. Pierce, Luna Sun, Jinglin Zhong, Meghan Feely, Jonathan I. Silverberg
Journal: Journal of the American Academy of Dermatology (2022)
33217 Mobile device digital photography for teledermatology consultation: Real-life situations
Authors: Chudapa Sereeaphinan, Pattriya Chanyachailert, Sumanas Bunyaratavej, Charussri Leeyaphan, Supisara Wongdama, Sanchai Sombatmaithai
Journal: Journal of the American Academy of Dermatology (2022)
32938 Guselkumab treatment modulates genes differentially expressed in blood samples of patients with psoriatic arthritis vs healthy controls in two phase 3 clinical trials (DISCOVER-1 and -2)
Authors: Stefan Siebert, Kristen M. Sweet, Christopher T. Ritchlin, Elizabeth C. Hsia, Alexa P. Kollmeier, Ya-Wen Yang, Xie L. Xu, Qingxuan Song, Michelle Miron
Journal: Journal of the American Academy of Dermatology (2022)
Neoadjuvant Cemiplimab for Stage II to IV Cutaneous Squamous-Cell Carcinoma
Authors: Neil D. Gross, David M. Miller, Nikhil I. Khushalani, Vasu Divi, Emily S. Ruiz, Evan J. Lipson, Friedegund Meier, Yungpo B. Su, Paul L. Swiecicki, Jennifer Atlas, Jessica L. Geiger, Axel Hauschild, Jennifer H. Choe, Brett G.M. Hughes, Dirk Schadendorf, Vishal A. Patel, Jade Homsi, Janis M. Taube, Annette M. Lim, Renata Ferrarotto, Howard L. Kaufman, Frank Seebach, Israel Lowy, Suk-Young Yoo, Melissa Mathias, Keilah Fenech, Hyunsil Han, Matthew G. Fury, Danny Rischin
Journal: New England Journal of Medicine (2022)

In a pilot study involving patients with cutaneous squamous-cell carcinoma, a high percentage of patients had a pathological complete response with the use of two doses of neoadjuvant cemiplimab before surgery. Data from a phase 2 study are needed to confirm these findings.
Incidence of new onset glomerulonephritis after SARS-CoV-2 mRNA vaccination is not increased
Authors: Matthias Diebold, Eleonore Locher, Philipp Boide, Annette Enzler-Tschudy, Anna Faivre, Ingeborg Fischer, Birgit Helmchen, Helmut Hopfer, Min Jeong Kim, Solange Moll, Giliane Nanchen, Samuel Rotman, Charalampos Saganas, Harald Seeger, Andreas D. Kistler
Journal: Kidney International (2022)

Numerous cases of glomerulonephritis manifesting shortly after SARS-CoV-2 vaccination have been reported, but causality remains unproven. Here, we studied the association between mRNA-based SARS-CoV-2 vaccination and new-onset glomerulonephritis using a nationwide retrospective cohort and a case-cohort design. Data from all Swiss pathology institutes processing native kidney biopsies served to calculate incidence of IgA nephropathy, pauci-immune necrotizing glomerulonephritis, minimal change disease, and membranous nephropathy in the adult Swiss population. The observed incidence during the vaccination campaign (January to August 2021) was not different from the expected incidence calculated using a Bayesian model based on the years 2015 to 2019 (incidence rate ratio 0.86, 95% credible interval 0.73-1.02) and did not cross the upper boundary of the 95% credible interval for any month. Among 111 patients 18 years and older with newly diagnosed glomerulonephritis between January and August 2021, 38.7% had received at least one vaccine dose before biopsy, compared to 39.5% of the general Swiss population matched for age and calendar-time. The estimated risk ratio for the development of new-onset biopsy-proven glomerulonephritis was not significant at 0.97 (95% confidence interval 0.66-1.42) in vaccinated vs. unvaccinated individuals. Patients with glomerulonephritis manifesting within four weeks after vaccination did not differ clinically from those manifesting temporally unrelated to vaccination. Thus, vaccination against SARS-CoV-2 was not associated with new-onset glomerulonephritis in these two complementary studies with most temporal associations between SARS-CoV-2 vaccination and glomerulonephritis likely coincidental.
Multi-omics Uncovering Different Faces of Clear Cell Ovarian Cancer
Authors: Stephanie Lheureux
Journal: Clinical Cancer Research (2022)

Summary The diagnosis of clear cell ovarian cancer relies on expert histopathology review. Further characterization from deep genomic and transcriptomic analyses can identify different subgroups. International collaboration is required to define the clinical impact and therapy opportunities in these specific subclassifications. See related article by Bolton et al., p. 4947
Impact of HbA1c Followed 32 Years From Diagnosis of Type 1 Diabetes on Development of Severe Retinopathy and Nephropathy: The VISS Study
Authors: Hans J. Arnqvist, Malin C. Westerlund, Mats Fredrikson, Johnny Ludvigsson, Maria Nordwall
Journal: Diabetes Care (2022)

OBJECTIVE To evaluate HbA1c followed from diagnosis, as a predictor of severe microvascular complications (i.e., proliferative diabetic retinopathy [PDR] and nephropathy [macroalbuminuria]). RESEARCH DESIGN AND METHODS In a population-based observational study, 447 patients diagnosed with type 1 diabetes before 35 years of age from 1983 to 1987 in southeast Sweden were followed from diagnosis until 2019. Long-term weighted mean HbA1c (wHbA1c) was calculated by integrating the area under all HbA1c values. Complications were analyzed in relation to wHbA1c categorized into five levels. RESULTS After 32 years, 9% had no retinopathy, 64% non-PDR, and 27% PDR, and 83% had no microalbuminuria, 9% microalbuminuria, and 8% macroalbuminuria. Patients with near-normal wHbA1c did not develop PDR or macroalbuminuria. The lowest wHbA1c values associated with development of PDR and nephropathy (macroalbuminuria) were 7.3% (56 mmol/mol) and 8.1% (65 mmol/mol), respectively. The prevalence of PDR and macroalbuminuria increased with increasing wHbA1c, being 74% and 44% in the highest category, wHbA1c &amp;gt;9.5% (&amp;gt;80 mmol/mol). In comparison with the follow-up done after 20–24 years’ duration, the prevalence of PDR had increased from 14 to 27% and macroalbuminuria from 4 to 8%, and both appeared at lower wHbA1c values. CONCLUSIONS wHbA1c followed from diagnosis is a very strong biomarker for PDR and nephropathy, the prevalence of both still increasing 32 years after diagnosis. To avoid PDR and macroalbuminuria in patients with type 1 diabetes, an HbA1c &amp;lt;7.0% (53 mmol/mol) and as normal as possible should be recommended when achievable without severe hypoglycemia and with good quality of life.
Discovery of the radio-protecting effect of Ecliptae Herba, its constituents and targeting p53-mediated apoptosis in vitro and in vivo
Authors: Jiang Wu, Wenfeng Gou, Zhiyun Wang, Huajie Chang, Deguan Li, Wenbin Hou, Changxiao Liu
Journal: Acta Pharmaceutica Sinica B (2022)

Radiation protection drugs are often accompanied by toxicity, even amifostine, which has been the dominant radio-protecting drug for nearly 30 years. Furthermore, there is no therapeutic drug for radiation-induced intestinal injury (RIII). This paper intends to find a safe and effective radio-protecting ingredient from natural sources. The radio-protecting effect of Ecliptae Herba (EHE) was discovered preliminarily by antioxidant experiments and the mouse survival rate after 137Cs irradiation. EHE components and blood substances in vivo were identified through UPLC‒Q-TOF. The correlation network of "natural components in EHE-constituents migrating to blood-targets-pathways" was established to predict the active components and pathways. The binding force between potential active components and targets was studied by molecular docking, and the mechanism was further analyzed by Western blotting, cellular thermal shift assay (CETSA), and ChIP. Additionally, the expression levels of Lgr5, Axin2, Ki67, lysozyme, caspase-3, caspase-8,8-OHdG, and p53 in the small intestine of mice were detected. It was found for the first time that EHE is active in radiation protection and that luteolin is the material basis of this protection. Luteolin is a promising candidate for RⅢ. Luteolin can inhibit the p53 signaling pathway and regulate the BAX/BCL2 ratio in the process of apoptosis. Luteolin could also regulate the expression of multitarget proteins related to the same cell cycle.
On-demand integrated nano-engager converting cold tumors to hot via increased DNA damage and dual immune checkpoint inhibition
Authors: Xiaoqing Liu, Shuang Liang, Xiao Sang, Lili Chang, Shunli Fu, Han Yang, Huizhen Yang, Yongjun Liu, Na Zhang
Journal: Acta Pharmaceutica Sinica B (2022)

Cancer immunotherapy has become a promising strategy. However, the effectiveness of immunotherapy is restricted in "cold tumors" characterized with insufficient T cells intratumoral infiltration and failed T cells priming. Herein, an on-demand integrated nano-engager (JOT-Lip) was developed to convert cold tumors to hot via "increased DNA damage and dual immune checkpoint inhibition" strategy. JOT-Lip was engineered by co-loading oxaliplatin (Oxa) and JQ1 into liposomes with T-cell immunoglobulin mucin-3 antibodies (Tim-3 mAb) coupled on the liposomal surface by metalloproteinase-2 (MMP-2)-sensitive linker. JQ1 inhibited DNA repair to increase DNA damage and immunogenic cell death (ICD) of Oxa, thus promoting T cells intratumoral infiltration. In addition, JQ1 inhibited PD-1/PD-L1 pathway, achieving dual immune checkpoint inhibition combining with Tim-3 mAb, thus effectively promoting T cells priming. It is demonstrated that JOT-Lip not only increased DNA damage and promoted the release of damage-associated molecular patterns (DAMPs), but also enhanced T cells intratumoral infiltration and promoted T cell priming, which successfully converted cold tumors to hot and showed significant anti-tumor and anti-metastasis effects. Collectively, our study provides a rational design of an effective combination regimen and an ideal co-delivery system to convert cold tumors to hot, which holds great potential in clinical cancer chemoimmunotherapy.
Endotrophin as a Marker of Complications in a Type 2 Diabetes Cohort
Authors: Ninna Hahn Tougaard, Alexandra Louise Møller, Pernille Falberg Rønn, Tine Willum Hansen, Federica Genovese, Morten Asser Karsdal, Daniel Guldager Kring Rasmussen, Peter Rossing
Journal: Diabetes Care (2022)

OBJECTIVE We investigated endotrophin, a profibrotic signaling molecule reflecting collagen VI formation, in serum and urine as risk marker for complications to type 2 diabetes. RESEARCH DESIGN AND METHODS Endotrophin was measured in 774 individuals with type 2 diabetes. Outcomes included a composite kidney end point, first major adverse cardiovascular event (MACE), mortality, progression of albuminuria, incident heart failure, and sight-threatening eye disease. Adjusted Cox proportional hazards models were applied. RESULTS Doubling of serum endotrophin was associated with the kidney end point (n = 49; hazard ratio 1.80 [95% CI 1.13–2.87]), first MACE (n = 66; 1.54 [1.04–2.28]), mortality (n = 156; 1.69 (1.31–2.19]), and incident heart failure (n = 42; 1.63 [1.02–2.60]). A doubling of urine endotrophin was associated with progression of albuminuria (n = 85; 1.20 [1.04–1.39]). CONCLUSIONS Serum endotrophin was a risk marker for mortality and kidney and cardiovascular complications in type 2 diabetes. Urine endotrophin was a marker for albuminuria progression.
Enhancing the therapeutic efficacy of nanoparticles for cancer treatment using versatile targeted strategies
Authors: Hailong Tian, Tingting Zhang, Siyuan Qin, Zhao Huang, Li Zhou, Jiayan Shi, Edouard C. Nice, Na Xie, Canhua Huang, Zhisen Shen
Journal: Journal of Hematology & Oncology (2022)

Poor targeting of therapeutics leading to severe adverse effects on normal tissues is considered one of the obstacles in cancer therapy. To help overcome this, nanoscale drug delivery systems have provided an alternative avenue for improving the therapeutic potential of various agents and bioactive molecules through the enhanced permeability and retention (EPR) effect. Nanosystems with cancer-targeted ligands can achieve effective delivery to the tumor cells utilizing cell surface-specific receptors, the tumor vasculature and antigens with high accuracy and affinity. Additionally, stimuli-responsive nanoplatforms have also been considered as a promising and effective targeting strategy against tumors, as these nanoplatforms maintain their stealth feature under normal conditions, but upon homing in on cancerous lesions or their microenvironment, are responsive and release their cargoes. In this review, we comprehensively summarize the field of active targeting drug delivery systems and a number of stimuli-responsive release studies in the context of emerging nanoplatform development, and also discuss how this knowledge can contribute to further improvements in clinical practice.